Chronic Fructose Substitution for Glucose or Sucrose in Food or Beverages and Metabolic Outcomes: An Updated Systematic Review and Meta-Analysis.

Despite the publication of several of meta-analyses in recent years, the effects of fructose on human health remains a topic of debate. We previously undertook two meta-analyses on post-prandial and chronic responses to isoenergetic replacement of fructose for sucrose or glucose in food or beverages (Evans et al. 2017, AJCN 106:506-518 & 519-529). Here we report on the results of an updated search with a complete re-extraction of previously identified studies and a new and more detailed subgroup-analysis and meta-regression. We identified two studies that were published after our previous analyses, which slightly altered effect sizes and conclusions. Overall, the isoenergetic substitution of fructose for glucose resulted in a statistically significant but clinically irrelevant reduction in fasting blood glucose, insulin, and triglyceride concentrations. A subgroup analysis by diabetes status revealed much larger reductions in fasting blood glucose in people with impaired glucose tolerance and type 2 diabetes. However, each of these subgroups contained only a single study. In people with a healthy body mass index, fructose consumption was associated with statistically significant, but clinically irrelevant reductions in fasting blood glucose and fasting blood insulin. Meta-regression of the outcomes by a number of pre-identified and